REM sleep deprivation produces a motivational deficit for food reward that is reversed by intra-accumbens amphetamine in rats.

Abstract

Prolonged sleep deprivation in rats produces a characteristic syndrome of increase in food intake accompanied by, paradoxically, decrease in weight, suggesting a potential alteration in motivation for food reward. Using the multiple platform method to produce REM sleep deprivation (REMSD), we investigated the effect of REMSD on motivation for food reinforcement with a progressive ratio operant task, which yields a measure of the motor effort that a hungry animal is willing to expend to obtain food (the point at which the animal quits responding is termed the "break-point"). We found that REMSD rats decreased the break point for sucrose pellet reinforcement in comparison to controls, as revealed by a within-session decline in responding. This behavioral deficit is similar to that observed in rats with diminished dopamine transmission within the nucleus accumbens (Acb), and, considering that stimulants are frequently used in the clinical setting to reverse the effects of sleepiness, we examined the effect of systemic or intra-Acb amphetamine on break point in REMSD rats. Animals were given either systemic or intra-Acb amphetamine injections on days 3 and 5 of REMSD. Systemic amphetamine (0.1, 0.5, or 2.5mg/kg) did not increase break point in REMSD rats. In contrast, intra-Acb infusions of amphetamine (1, 10, or 30μg/0.5μl bilaterally) reversed the REMSD-induced suppression of progressive ratio responding. Specifically, the two higher doses of intra-Acb amphetamine were able to prolong responding within the session (resulting in an increased break point) on day 3 of REMSD while only the highest dose was sufficient following 5 days of REMSD. These data suggest that decreased motivation for food reward caused by REMSD may result from a suppression of dopamine function in the Acb.

The effect of REMSD on break point in a progressive ratio 2 operant task. Error bars represent one SEM. Note that the y-axis scales differ in A and B. Furthermore, baseline is an average of the three previous days preceding the period of REMSD. (A) Mean break points in 30-min sessions are shown for sleep-deprived (D), apparatus control (C), and home cage (H) groups fed ad libitum. *P < 0.05 for the C vs. H comparison. #P < 0.05 for D vs. H comparison. (B) Within-session responding for sessions on days 2–5 of REMSD in PR2 fed ad libitum. For the sake of clarity, the mean numbers of responses for each group are shown in three-minute bins across the 30-minute session.

The effect of systemic amphetamine on break point in REMSD. Baseline is an average of the three previous days preceding the period of REMSD. Various doses of systemic amphetamine were administered on days 3 and 5 of REMSD to the (A) home cage and (B) REM sleep-deprived animals. Administration of amphetamine is denoted with an arrow. Error bars represent one SEM.

Within-session responding for the all groups on days 2–5 of REMSD. Error bars represent one SEM. Note that scale on y-axis differs between home cage and REMSD groups. Testing days were separated according to systemic amphetamine treatment, for the sake of clarity. Responding for the home cage animals are shown in A and B in which the animals received no treatment on days 2 and 4 (A), and were administered systemic amphetamine on days 3 and 5 (B). Responding rates for the REM sleep-deprived rats are shown in C and D in which the animals did not receive amphetamine treatment on days 2 and 4 (C), and were administered systemic amphetamine on days 3 and 5 (D).

The effect of intra-nucleus accumbens amphetamine on break point in REMSD. Baseline is an average of the three previous days preceding the period of REMSD. Various doses of intra-Acb amphetamine were administered on days 3 and 5 of REMSD to the (A) home cage and (B) REM sleep-deprived animals. Intra-Acb administration of amphetamine is denoted with an arrow. Error bars represent one SEM.

Within-session responding for the all groups on days 2–5 of REMSD. Error bars represent one SEM. Note that scale on y-axis differs between home cage and REMSD groups. Testing days were separated according to systemic amphetamine treatment, for the sake of clarity. Within-session lever presses for the home cage animals are shown in A and B; the animals received no treatment on days 2 and 4 (A), and were given intra-Acb amphetamine on days 3 and 5 (B). Responding for the REM sleep-deprived rats is shown in C and D; the animals did not receive amphetamine treatment on days 2 and 4 (C), and were given intra-Acb amphetamine on days 3 and 5 (D).